Myotonic dystrophy type 2 (DM2) is caused by an expansion of CCTG repeats in the zinc-finger protein gene (ZNF9). Transcribed CCUG repeats sequester muscleblind-like protein 1 (MBNL1), an important alternative splicing regulator, preventing its normal function, leading to the disease phenotype. We describe a series of ligands that disrupt the MBNL1–r(CCUG)_n interaction as potential lead agents for developing DM2 therapeutics. A previously reported triaminopyrimidine–acridine conjugate was a moderate inhibitor in vitro, however it proved to be poorly water-soluble and not cell-permeable. To improve its therapeutic potential, the new set of ligands maintained the key triaminopyrimidine recognition unit but replaced the acridine intercalator with a bisamidinium groove binder. The optimized ligands exhibit low micromolar inhibition potency to MBNL1–r(CCUG)₈. Importantly, the ligands are the first to show the ability to disrupt the MBNL1–r(CCUG)_n foci in DM2 model cell culture and exhibit low cytotoxicity.

Supramolecular polymer chemistry has emerged as a major research focus within polymer science, because of the potential to improve material properties, through the combination of noncovalent interactions and synthetic polymers. As a supramolecular handle, the most useful noncovalent interaction is hydrogen bonding, which has been used extensively, because of advantages such as synthetic accessibility, directionality, fidelity, and, most importantly, responsiveness to external stimuli. This review introduces recent advances in the development of hydrogen bonding modules that can be useful for creating a variety of supramolecular polymers. Furthermore, we present selected examples of hydrogen bonded supramolecular polymers from the literature, by dividing them into three categories: supramolecular polymers assembled from small molecules, and main-chain and side-chain supramolecular polymers.

The synthesis and photophysical properties of water-soluble, fluorescent polyglycerol-dendronized perylenediimides 1–4 are reported. The polyglycerol dendrons, which are known to be highly biocompatible, are found to confer high water-solubility on the perylenediimide in aqueous media while retaining its excellent fluorescent properties. Furthermore, intramolecular crosslinking of the polyglycerol dendrons using the ring-closing metathesis reaction not only enhances the photostability but also reduces the size of perylenediimide-cored dendrimers. The permeability of the various dendritic shells is probed using heavy metal ion quenchers and compared to non-dendritic but water-soluble perylenediimide 5.

Cored polymeric nanoparticles were prepared using an adenosine template and allylated hyperbranched polyglycerols (HPGs). The HPGs contained a single alkyne that was capable of 1,3-dipolar cycloaddition with a decaazido adenosine template to facilitate the rapid synthesis of HPGs containing a large number of allyl end-groups. Ring closing metathesis (RCM) mediated cross-linking at high dilution using a Hoveyda-Grubbs catalyst produced single polymer nanoparticles containing a single template. These particles were rendered water-soluble through treatment with osmium tetroxide and NMO co-oxidant. After hydrolytic removal of the template, the nanoparticles were tested for their ability to bind a variety of nucleosides and nucleobases and showed a preference for purine bases over pyrimidine bases. This is the first reported use of hyperbranched polymers for the synthesis of monomolecularly imprinted polymers (mMIPs) as well as the first time monomolecular imprinting has been applied to a homogeneous aqueous system.